The present invention concerns the heterocyclic carbon compounds of the 1,4-dihydropyridine class with a 3-carboxylate or carboxamido group linked to an aryloxypropanolamine moiety. These compounds possess bio-affecting properties.
A substantial body of prior art has evolved over the last decade involving compounds of 4-aryl-1,4-dihydropyridine series which have calcium antagonist properties and are useful in the treatment of cardiovascular diseases. These calcium blocking effects appear to mediate vasodilation making these compounds useful in treating angina and hypertension. These structures are typified by nifedipine ##STR1## chemically. 4-nitrophenyl)-2,6-dimethyl-3,5-dicarbomethoxy-1,4-dihydropyridine. Nifedipine and some related 4-aryl-1,4-dihydropyridines are the subject of U.S. Pat. No. 3,485,847 issued Dec. 23, 1969. Numerous subsequent patents have been granted covering 1,4-dihydropyridines in which other substituent groups have been incorporated as the various ring positions of the dihydropyridine moiety via a diversity of chemical bonding groups.
It is currently recognized that dihydropyridine calcium blockers and beta-adrenergic blockers in concert can evoke a greater hemodynamic response than either of the two agents administered individually. Therefore, an object of the instant invention was to design a therapeutic agent combining beta-adrenergic blocking properties with the vasodilation of a calcium blocking agent in a single molecular structure. As far as applicants are aware, the only example of a single molecular structure incorporating both an aryloxypropanolamine and nifedipine-like dihydropyridine structural moiety has been reported by Baldwin, et al., J. Med. Chem., 24, pp. 628-631 (1981). An example of this series of compounds is shown below as Formula 2. ##STR2## These compounds, however, did not possess sufficient .beta.-block activity to warrant further interest.
As can be seen, the 4-aryl group of the standard dihydropyridine structure also serves as the aryl group for the aryloxypropanolamine moiety. The compounds of Baldwin, et al. are easily distinguishable structurally over the compounds of the instant invention.
Other related art, although of limited relevancy, can be typified in general by compounds of structure 3 as reported by Araki, et al., European Patent Application 60,897. ##STR3## In structure 3, R.sup.1, R.sup.4 and Ar.sup.1 represent a number of substituent groups which have been previously defined in the voluminous dihydropyridine literature. The groups R.sup.2 and R.sup.3 may be lower alkyl or aralkyl. These compounds differ significantly from those of the instant invention in that there is no aryloxypropanolamine moiety in the Araki, et al. structure.
In essence, there is nothing in the prior art of which applicants are aware which anticipates or suggests the compounds of the present invention.